Pharmacokinetics, Pharmacodynamics, and Safety of NANOKINE Compared With Eprex 4000 U in Healthy Volunteers

Официальное название

A Randomized, Two-treatment, Two-period, Crossover, Single-dose, Subcutaneous Injection Study Comparing the Pharmacokinetics, Pharmacodynamics, and Safety of Nanokine Manufactured by Nanogen Pharmaceutical Biotechnology Joint Stock Company With Eprex 4000 U Manufactured by Cilag AG in Healthy Volunteers

Обзор

This clinical trial aims to compare the pharmacokinetic (PK), pharmacodynamic (PD) parameters, and safety between Nanokine of Nanogen Pharmaceutical Joint Stock Company and Eprex® of Janssen Cilag Ltd on healthy male volunteers. The biosimilarity of erythropoietin (EPO) between Nanokine (test) and Eprex® (comparator) was evaluated in a randomized, two-treatment, two-period, crossover, single-dose study. Subjects received a 4,000 IU subcutaneous dose of either formulation, followed by the alternate after a 28-day washout. Key pharmacokinetic (PK) parameters, Cmax and AUCinf, were assessed, with geometric mean ratios/GMR (90% CI) falling within the regulatory range (0.80-1.25). Pharmacodynamic (PD) marker (reticulocyte count) need to show comparable effects. Safety evaluation (adverse events and serious adverse events, other safety assessments such as vital signs, testing, and examination) supports their interchangeability in clinical use.

Подробное описание

Erythropoietin (EPO) is a glycoprotein hormone essential for red blood cell (RBC) formation, primarily produced in the kidneys. Recombinant human erythropoietin (rHuEPO) or erythropoiesis-stimulating agents (ESAs) are used to treat anemia in chronic renal failure, chemotherapy-induced anemia, and to reduce transfusion needs in surgery.

Nanokine, currently considered as a follow-on biological product of Eprex® developed by Nanogen Biopharmaceutical JSC, is produced in CHO cells. This study evaluates the bioequivalence of Nanokine and Eprex® in healthy volunteers, comparing pharmacokinetics (PK), pharmacodynamics (PD), and safety.

A randomized, open-label, single-dose, two-sequence crossover trial is conducted in 44 healthy male volunteers (aged 19-45 years, BMI 18.0-28.0 kg/m²). Participants received a 4,000 IU subcutaneous injection of either Eprex® or Nanokine, followed by the alternate after a 28-day washout. Blood samples for PK analysis were taken at multiple time points up to 144 hours postdose, while PD markers (reticulocytes) were measured up to 312 hours postdose.

The purpose of this clinical study is to evaluate and compare the pharmacokinetics, pharmacodynamics, and safety profile of NANOKINE (manufactured by Nanogen Pharmaceutical Biotechnology Joint Stock Company) with Eprex 4000 U (manufactured by Cilag AG).

This is a randomized, two-treatment, two-period, crossover study involving a single-dose subcutaneous injection administered to healthy volunteers.

Participants will undergo a comprehensive screening process to ensure they are in good health, meet the required age range of 18 to 45 years, and fall within the specified body weight and body mass index (BMI) criteria. Eligible subjects will be randomly assigned to receive the study treatments across two distinct periods, separated by a washout phase, to evaluate how each product behaves in the body and to assess their overall safety and tolerability.

Pharmacokinetics (PK) Statistical Hypotheses:

* Null Hypothesis (H0): The 90% confidence interval of the geometric mean ratio (GMR) between NANOKINE and Eprex 4000 U for the log-transformed data of AUC0-t and Cmax falls outside the bioequivalence limits of 80.00% to 125.00%. * Alternative Hypothesis (H1): The 90% confidence interval of the GMR falls within the limits of 80.00% to 125.00% for the log-transformed data of both AUC0-t and Cmax, thereby demonstrating pharmacokinetic equivalence between the two formulations.

Pharmacodynamics (PD) Statistical Hypotheses:

* Null Hypothesis (H0): The 90% confidence interval of the geometric mean ratio (GMR) between NANOKINE and Eprex 4000 U for the log-transformed data of AUC0-t and Cmax of reticulocyte (RET) count falls outside the bioequivalence limits of 80.00% to 125.00%. * Alternative Hypothesis (H1): The 90% confidence interval of the GMR falls within the limits of 80.00% to 125.00% for the log-transformed data of both AUC0-t and Cmax of reticulocyte (RET) count, thereby demonstrating pharmacodynamic equivalence between the two formulations.

This study is conducted at the Center for Clinical Pharmacology, Hanoi Medical University, in accordance with the Vietnam Biomedical Research, Ethics, and Regulatory Guidelines.

Вмешательства

• Биопрепарат Erythropoietin alfa
  Experimental drug: Nanokine 4000 IU, prefilled syringe, subcutaneous injection Manufactured: Nanogen Biopharmaceutical JSC. Arm 1 (22 volunteers): Nanokineinjection 4000 IU will be administered subcutaneously on Day 1, and after a 28-day washout period, Eprex® injection 4000 IU will be administered subcutaneously on Day 29.
• Биопрепарат Erythropoietin alfa
  Comparator drug: Eprex® 4000 IU, prefilled syringe, subcutaneous injection Manufactured: Janssen-Cilag Ltd Arm 2 (22 volunteers): Eprex® injection 4000 IU will be administered subcutaneously on Day 1, and after a 28-day washout period, Eprex injection 4000 IU will be administered subcutaneously on Day 29. Total: 44 participants will be recruited in the trial.

Первичные конечные точки

• AUC0-t [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• Cmax [Срок оценки: Pre-dose (30, 20, and 10 minutes before injection) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after injection).]
• AUC0-t of RET [Срок оценки: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)]
• Cmax of RET [Срок оценки: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)]

Вторичные конечные точки (9)

• AUC0-inf [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• Tmax [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• T1/2 [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• CL.obs [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• Vz.obs [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration).]
• Lambda.z [Срок оценки: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)]
• RBC Count [Срок оценки: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)]
• Hb [Срок оценки: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)]
• Adverse events [Срок оценки: Baseline to 312 hours after the crossover dose]

Критерии участия

Критерии включения

• Male, aged 18 to 45 years.
• Body weight 50 kg - 70 kg, BMI 18 - 28 kg/m², calculated per Metropolitan Index 1983 for adults.
• At the time of screening, the subject is determined to be healthy by the investigator through a general clinical examination.
• Laboratory test results for ECG, hematology and biochemistry (fasting glucose, urea, AST, ALT, creatinine) are within normal limits or assessed by the investigator as normal/eligible for study participation.
• Screening test results:

• Hemoglobin 125-175 g/L;
• Vitamin B12 200-300 pg/mL;
• Ferritin 22-400 ng/mL;
• Transferrin 200-360 mg/dL;
• Albumin 35-52 g/L;
• Reticulocytes, red blood cells, and platelets within normal range;
• Negative urine drug screen;
• Negative HBsAg, anti-HCV and HIV.
• Voluntarily participates in the study and has signed the informed consent form.

Критерии исключения

• Lacks civil act capacity.
• History of severe allergic reaction or anaphylaxis to biological products.
• Use of Erythropoiesis Stimulating Agents (ESAs) or immunoglobulins within 3 months prior to screening.
• History of seizures, epilepsy, or current disorders of the cardiovascular, respiratory, hepatic, renal, gastrointestinal, immune, hematologic, endocrine, nervous system, or psychiatric illness (as determined by the examining physician).
• Recent illness within 2 weeks prior to screening (based on medical history and clinical examination).
• History of blood loss >450 mL or blood donation within 28 days prior to the first scheduled dose.
• History of illicit drug use.
• Recent history of alcohol abuse (defined as regular alcohol consumption within 6 months prior to screening, with average weekly intake >21 units/week. One unit equals 8 g ethanol, equivalent to: 240 mL (half a glass) of beer, or 100 mL (1 glass) of wine, or 25 mL (1 shot) of spirits).
• Recent history of tobacco abuse (defined as smoking on average >10 cigarettes/day within 3 months prior to screening, or inability to abstain from smoking throughout the study period).
• Excessive caffeine consumption (more than 5 cups of coffee per day).
• Special dietary habits or inability to consume meals provided by the study site.
• Currently participating in another clinical study, or has participated in a clinical study with another investigational product within the last 3 months.
• Planning to conceive during the study period or unwilling to use contraception throughout the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06919861 · NNG31

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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